Age, Education Years, and Biochemical Factors Are Associated with Selective Neuronal Changes in the Elderly Hippocampus

Abstract

Brain aging involves regional alterations of specific cellular subpopulations in the human hippocampus: a network hub for memory consolidation. The present study investigates whether age, sex, education years, and the concentration of neuropathological and inflammatory proteins influence neuronal-type marker expression in the elderly hippocampus. We analyzed the digital images (1 µm/pixel) of postmortem hippocampal sections from 19 non-demented individuals (from 78 to 99 years). This material was obtained from the “Aging Dementia and TBI Study” open database. Brain samples were processed through in situ hybridization (ISH) for the immunodetection of VGLUT1 (glutamatergic transporter) and GAT1 (GABAergic transporter) and mRNAs and Luminex protein quantifications. After image acquisition, we delineated the dentate gyrus, CA 3/2, and CA1 hippocampal subdivisions. Then, we estimated the area fraction in which the ISH markers were expressed. Increased VGLUT1 was observed in multiple hippocampal subfields at late ages. This glutamatergic marker is positively correlated with beta-amyloid and tau proteins and negatively correlated with interleukin-7 levels. Additionally, education years are positively correlated with GAT1 in the hippocampus of elderly women. This GABAergic marker expression is associated with interferon-gamma and brain-derived neurotrophic factor levels. These associations can help to explain how hippocampal sub-regions and neurotransmitter systems undergo distinct physiological changes during normal aging.

Alterations in Human Hippocampus Subregions across the Lifespan: Reflections on White Matter Structure and Functional Connectivity

“…Interestingly, hippocampus FC appeared to increase in late ages, which also seemed to occur with the expression of some hippocampal cell markers. On the one hand, it has been shown that brain aging involved regional alterations of specific cellular subpopulations in the human hippocampus [ 62 , 63 ]. For example, increased glutamatergic transporter was observed in multiple hippocampal subfields at late ages.…”

“…For example, increased glutamatergic transporter was observed in multiple hippocampal subfields at late ages. This glutamatergic marker was positively correlated with beta-amyloid and tau proteins [ 63 ]. The GA1 hippocampal area was also positively correlated with the concentrations of interferon-gamma and brain-derived neurotrophic factor (BDNF).…”

Advances in IL-7 Research on Tumour Therapy

“…Additionally, IL-7 has been associated with dysregulated energy metabolism, leading to malnutrition in cancer patients [ 86 ]. There is also evidence that IL-7 may affect the mental state of cancer patients by influencing neurotransmitter levels, leading to psychological problems such as anxiety and depression, further reducing the patient’s quality of life [ 87 ].…”